Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the majority of adult and pediatric patients with AIDS, hematologic abnormalities including leukopenia, anemia, and thrombocytopenia are commonly observed. In addition to these findings, changes in hematopoietic progenitor cells occur, including a reduction of multipotential-forming units, granulocyte-macrophages, macrophage as well as eosinophil colony-forming units, and bone marrow erythroid burst-forming units. This study examined alterations in human fetal liver hematopoiesis in 2nd trimester abortuses from human immunodeficiency virus (HIV)-seropositive women. The differentiation and growth potential of hematopoietic cells in vitro were monitored. Upon initial isolation, some populations of liver hematopoietic cells from abortuses of HIV-seropositive women were significantly decreased when compared to age-matched samples from fetuses of normal females including the percentage of early T cells [cluster of differentiation (CD)2], B cells (CD19), and early monocytes (CD14). A decrease in multipotent progenitors (CD34), myelomonocytes (CD33), and panleukocytes (CD45) was also observed. In contrast, after 21 d in culture, cells from HIV abortuses demonstrated an increase in the percentage of CD14 cells when stimulated with erythropoietin and granulocyte-monocyte colony-stimulating factor, as well as an increase in CD45 phenotype after exposure to granulocyte-monocyte colony-stimulating factor alone. These samples showed a persistence of erythropoietic elements (transferrin and CD36 phenotype) when compared to normal controls. No significant difference in the in vitro growth of hematopoietic progenitors (bone marrow erythroid burst-forming units, granulocyte-macrophage colony-forming units, and multipotential forming units) between these samples and normal controls was found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in human fetal hematopoiesis are associated with maternal HIV infection. 150 4

A murine monoclonal antibody (MoAb) F101.01 reacting with the T cell receptor (TCR)-T3 complex is presented. Immunohistological studies showed that F101.01 specifically stains T-zone lymphocytes in lymph nodes, tonsils, and splenic tissue. Two-colour immunofluorescence and flow cytometry demonstrated co-expression of the antigen defined by F101.01 and the pan-T cell antigens defined by CD2, CD3, CD5, and CD7 antibodies. Cells stained with CD4 and CD8 antibodies were both included in the F101.01-positive population, whereas CD16-positive natural killer cells (NK), B cells (CD19 and CD20), and myeloid cells (CD13 and CD33) were excluded. The target antigen of F101.01 co-modulated with the CD3-defined antigen (T3) and the TCR recognized by the MoAb WT-31. CD3 antibody and WT-31 both blocked binding of F101.01. F101.01 precipitated the TCR-T3 complex from lysates of 125I-labelled peripheral blood mononuclear cells (PBMC) and HPB-ALL, when the lysate was prepared with a detergent (digitonin) that conserves the TCR-T3 complex. FACS analysis of T cells from a patient with a T cell immunodeficiency demonstrated that delta-TCS-1-CD3+CD4+ and delta-TCS-1-CD3+CD8+ cells were brightly F101.01+, whereas a large subpopulation of delta-TCS-1+CD3+CD4-CD8- cells were weakly F101.01+. We conclude that F101.01 recognizes a conformational epitope of the TCR-T3 complex and that it reacts with the alpha beta TCR-T3 and the gamma delta TCR-T3 complexes with different intensities.
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PMID:Characterization and expression of the human T cell receptor-T3 complex by monoclonal antibody F101.01. 296 42

Monocytes in a familial monocyte disorder, a recently recognized primary immunodeficiency syndrome, with impaired phagocytic functions were studied for their ability to produce interleukin 1 (IL-1) as well as the surface property. Monocytes from two children (siblings) with the disorder possessed CD11b, CD13, CD14, CD33, Ia and LFA-1/Mac-1/p150,95 beta subunit antigens as determined by flow cytometry. Electron microscopic cytochemistry showed that the monocytes had surface glycoproteins reactive with four representative lectins. The IL-1 production by monocytes was assayed in the two patients and compared with that in six children with primary immunodeficiency syndromes and some monocyte abnormalities; three had congenital neutropenia, two had hyper-IgE syndrome, and one had defective monocyte chemotaxis. Monocyte culture supernatants were prepared with stimulation by lipopolysaccharide or silica, and their IL-1 activity was measured by the mouse thymocyte-proliferation assay. The patients' monocytes were defective in IL-1 production: the values were less than 1.0% of the control monocyte values (n = 12) and were in contrast with those of congenital neutropenia monocytes of 186.2% to 204.3%. These results demonstrate a familial monocyte disorder which is characteristic among the immunodeficiency syndromes with regard to the defective IL-1 production and the impaired phagocytic functions.
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PMID:Defective interleukin-1 production in a familial monocyte disorder with a combined abnormality of mobility and phagocytosis-killing. 326 74

It has been recently reported that murine hematopoietic stem cells and progenitors express low levels of CD4. In this study, we have investigated by phenotypic and functional analysis whether the CD4 molecule was also present on human hematopoietic progenitors. Unfractionated marrow cells or immunomagnetic bead-purified CD34+ cells were analyzed by two-color fluorescence with an anti-CD4 and an anti-CD34 monoclonal antibody (MoAb). A large fraction (25% to 50%) of the CD34+ cells was weakly stained by anti-CD4 antibodies. Moreover, in further experiments analyzing the expression of CD4 in different subpopulations of CD34+ cells, we found that CD4 was predominantly expressed in phenotypically primitive cells (CD34+ CD38-/low CD71low Thy-1high, HLA-DR+/low). However, the presence of CD4 was not restricted to these primitive CD34+ cell subsets and was also detected in a smaller fraction of more mature CD34+ cells exhibiting differentiation markers. Among those, subsets with myelo-monocytic markers (CD13, CD33, CD14, and CD11b) have a higher CD4 expression than the erythroid or megakaryocytic subsets. In vitro functional analysis of the sorted CD34+ subsets in colony assays and long-term culture-initiating cell (LTC-IC) assays confirmed that clonogenic progenitors (colony-forming unit-granulocyte-macrophage, burst-forming unit-erythroid, and colony-forming unit-megakaryocyte) and LTC-IC were present in the CD4low population. However, most clonogenic progenitors were recovered in the CD4- subset, whereas the CD4low fraction was greatly enriched in LTC-IC. In addition, CD4low LTC-IC generated larger numbers of primitive clonogenic progenitors than did CD4- LTC-IC. These observations suggest that, in the progenitor compartment, the CD4 molecule is predominantly expressed on very early cells. The CD4 molecule present on CD34+ cells appeared identical to the T-cell molecule because it was recognized by three MoAbs recognizing different epitopes of the molecule. Furthermore, this CD4 molecule is also functional because the CD34+ CD4low cells are able to bind the human immunodeficiency virus (HIV) gp120. This observation might be relevant to the understanding of the mechanisms of HIV-induced cytopenias.
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PMID:Expression of CD4 by human hematopoietic progenitors. 754 75

In addition to CD4, the primary receptor to which the human immunodeficiency virus type 1 (HIV-1) binds, mononuclear phagocytes (monocytes) express three classes of Fc receptors for immunoglobulin G (Fc gamma R). We have previously shown that infection of monocytes by HIV-1 is inhibited when bispecific antibodies (BsAbs) are used to target the virus to either the type I, type II, or type III Fc gamma R on these cells. Infection of monocytes was not inhibited when HIV-1 was targeted to either human leukocyte antigen class I or CD33. We have extended these studies to examine the ability of BsAbs plus polymorphonuclear leukocytes (neutrophils, PMNs) and monocytes to reduce infectivity of HIV-1 to cells from the human T cell lymphoma line, H9. The production of HIV-1 following interaction of virus with BsAb and phagocytes was determined in an indicator cell assay by mixing BsAb, HIV-1, and phagocytes with uninfected H9 cells. Productive infection of H9 cells was quantitated on subsequent days by measuring p24 gag antigen levels in supernatants by enzyme-linked immunosorbent assay. Our findings show that the addition of interferon-gamma-activated PMNs or monocytes to cultures of HIV-1 plus H9 cells in the absence of BsAb results in a marked reduction in p24 levels equivalent to 85 to 90% of control levels. With the combination of BsAb (anti-Fc gamma RI x anti-gp120) plus IFN-gamma-activated phagocytes, levels of p24 in H9 cultures were below those at culture initiation. These findings demonstrate that IFN-gamma-activated phagocytes can affect the natural course of HIV-1 infection of T cells, a finding of potential clinical importance.
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PMID:Targeting HIV-1 to Fc gamma R on human phagocytes via bispecific antibodies reduces infectivity of HIV-1 to T cells. 812 Apr 55

Alveolar macrophages (AMs) harvested from 32 HIV-infected patients with respiratory problems (opportunistic pulmonary infections, n = 12; other lung disease, n = 20) and 13 healthy controls were stained with a panel of 15 monoclonal antibodies directed against surface antigens implicated in cell function. Antigen expression was quantified by flow cytometry and expressed as relative linear median fluorescence intensity (RLMFI). On AMs of patients, as compared with controls, there was a significant enhancement of HLA DP (12.1 +/- 1.5 vs 6.5 +/- 0.9, p = 0.01, M +/- SEM, RLMFI units), CD11b (3.4 +/- 0.5 vs 1.7 +/- 0.4, p = 0.014), CD11c (8.9 +/- 1.0 vs 4.8 +/- 0.8, p = 0.0046), CD14 (2.1 +/- 0.3 vs 1.0 +/- 0.2, p = 0.0009), and CD33 (1.7 +/- 0.1 vs 1.0 +/- 0.2, p = 0.0093). No significant differences could be established for HLA-DR (36.9 +/- 5.8 vs 30.9 +/- 7.5, NS), HLA-DQ (3.4 +/- 0.3 vs 3.1 +/- 0.6, NS), CD54 (1.9 +/- 0.3 vs 1.2 +/- 0.1, NS), CD13 (2.5 +/- 0.6 vs 1.5 +/- 0.3, NS), CD36 (1.4 +/- 0.2 vs 0.9 +/- 0.3, NS), CD71 (10.3 +/- 1.9 vs 8.9 +/- 1.8, NS), CD25 (0.8 +/- 0.0 vs 0.9 +/- 0.1, NS), 27E10 (1.1 +/- 0.1 vs 0.8 +/- 0.3, NS), RM3/1 (1.9 +/- 0.4 vs 1.5 +/- 0.4, NS), and CD4 (1.5 +/- 0.3 vs 1.0 +/- 0.0, NS). The expression of CD14 and CD11b, but not of HLA class II antigens and CD71, was increased in the smaller cell population compared with the larger, thus suggesting monocyte recruitment. The increased expression of HLA-DP, CD11c, CD14, and CD33 on the patients' AMs was independent of smoking habits. The degree of immunodeficiency as indicated by the absolute peripheral CD4 count, the character of HIV-related pulmonary disease, and the prophylactic use of pentamidine or zidovudine did not significantly modify the antigen expression pattern. It is concluded that HIV infection may lead, most probably indirectly, to enhanced expression of surface antigens by local upregulation and/or recruitment of monocytes from the peripheral circulation. The functional significance of enhanced marker expression requires further clarification.
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PMID:Expression of surface markers on alveolar macrophages from symptomatic patients with HIV infection as detected by flow cytometry. 818 14

Patients with human immunodeficiency virus-type 1-immune thrombocytopenic purpura (HIV-1-ITP) have elevated polyethylene glycol (PEG)-precipitable immune complexes (ICs) composed of IgG, IgM, and complement that are threefold to sevenfold higher than in healthy control subjects. These complexes contain anti-F (ab')2 as well as anti-idiotype antibodies versus anti-HIV-1gp120. Because anti-F (ab')2 and anti-idiotype antibodies correlate with thrombocytopenia (r = .83 [J Clin Invest 77:1756, 1986] and r = .90 [J Clin Invest 89:356, 1992], respectively) we studied the binding of ICs to platelets and monocytes as well as their role in platelet-monocyte rosette formation. ICs bind to platelets in a saturation-dependent manner (optimum at 10 micrograms/mL; 0.5% of serum conc). Binding to platelets could not be inhibited with platelet saturating concentrations of aggregated IgG or with monoclonal antibody (MoAb) IV.3 versus FcR gamma II. Platelet binding could be inhibited with Fab anti-C3, anti-Clq, or anti-C4 by 57%, 40%, and 46% respectively, not with control Fab (P < .001). Monocytes from HIV-1-ITP patients form rosettes with normal platelets 16.8 +/- 5.2 rosettes/100 monocytes compared with 4.8 +/- 0.8 control monocytes plus normal platelets (P = .009). Gel-washed HIV-1-ITP platelets formed 19 +/- 2.0 rosettes with U937 cells compared to 6.3 +/- 1.0 for normal platelets (P = 0.001). Arming of U937 cells with HIV-1-ITP ICs (5 micrograms/mL) formed 36.7 +/- 2.5 rosettes compared with 10.6 +/- 1.2 for control ICs (P < .01). Rosetting of armed U937 cells could be inhibited with MoAbs versus the alpha chains of CD11a (LFA-1), 11b (Mac-1), or 11c (p150,95) by 67%, 70%, and 61%, respectively (P < .007), whereas binding of ICs to U937 cells was unaffected. Isotype-matched control as well as MoAbs versus antigens on U937 cells (CD13, CD33) or the anti-FcR gamma II receptor had no effect. However, Fab fragments of polyclonal anti-C3 inhibited rosette formation by 78% (P < .01); control Fab had no effect. Thus, platelet-monocyte rosette formation is not Fc dependent. It is complement receptor dependent and requires the cooperation of all three leuCAM integrins.
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PMID:Role of leuCAM integrins and complement in platelet-monocyte rosette formation induced by immune complexes of human immunodeficiency virus-type 1-immune thrombocytopenic purpura patients. 848 17

Flow cytometry was used to assess CD4 expression in 62 consecutive bone marrow specimens from patients with a variety of clinical conditions. Using a lysed-whole-blood technique for labeling with monoclonal antibodies, two populations of CD4+ cells were identified within the lymphocyte/blast-cell fraction in 58 (94%) of these specimens. These consisted of (1) a population of T helper cells with high density expression of CD4 and (2) a second population of cells with low-density expression of CD4, which ranged from 1% to 36% of the gated cells. This latter population was present regardless of age, sex, or clinical condition including 21 of 21 specimens (100%) categorized as unremarkable bone marrows both morphologically and by flow cytometry and in four of four patients (100%) with human immunodeficiency virus-type 1 (HIV-1) infection. Coexpression of the erythroid lineage marker, glycophorin A, with the majority of cells in this second population was demonstrated in all 11 randomly selected samples using two-color flow cytometric analysis. These cells also expressed low levels of the myeloid markers, CD13 and CD33, but CD34 expression could not be demonstrated. These results provide evidence for expression of CD4 on cells of erythroid lineage in human marrow, and offer a potential mechanism for direct infection of erythroid precursor cells and deranged erythropoiesis in patients with HIV-1 infection.
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PMID:CD4 Expression by erythroid precursor cells in human bone marrow. 863 Mar 88

Monocytes and macrophages (Mo/Mphi) contribute to the pathogenesis of human immunodeficiency virus type 1 (HIV-1) infection. A successful hematopoietic stem/progenitor cell (HSPC)-based gene therapy strategy for HIV-1 disease must protect Mo/Mphi as well as T cells from HIV-1-related pathology. In this report, we demonstrate that RevM10-transduced HSPCs isolated from cytokine-mobilized peripheral blood give rise to Mo/Mphi suppressing replication of Mphi-tropic HIV-1 isolates. A Moloney murine leukemia virus (MoMLV)-based retroviral vector encoding a bicistronic mRNA co-expressing RevM10 and the murine CD8alpha' chain (Lyt2) was used to transduce HSPCs. Following transduction, these cells were expanded and differentiated by short-term culture in methylcellulose containing various cytokines. In vitro differentiated Mo/Mphi were enriched by fluorescence activated cell sorting (FACS) for the co-expressed transgene (Lyt2) and myelomonocytic (CD33, CD14) surface markers. HIV-1 replication of two Mphi-tropic isolates (JR-FL, BaL) was inhibited in Mo/Mphi expressing RevM10 and Lyt2 relative to control cells expressing only Lyt2 but no functional RevM10 gene product. Cell proliferation and expression of lineage-specific surface markers was not altered in transduced, in vitro differentiated Mo/Mphi cells. This study supports the feasibility of HSPC-based gene therapy as a future treatment for HIV-1 disease.
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PMID:Inhibition of human immunodeficiency virus type 1 replication in myelomonocytic cells derived from retroviral vector-transduced peripheral blood progenitor cells. 950 51

T lymphocyte dysfunction contributes to human immunodeficiency virus type 1 (HIV-1) disease progression by impairing antivirus cellular immunity. However, the mechanisms of HIV-1 infection-mediated T cell dysfunction are not completely understood. Here, we provide evidence that expansion of monocytic myeloid-derived suppressor cells (M-MDSCs) suppressed T cell function in HIV-1-infected individuals. We observed a dramatic elevation of M-MDSCs (HLA-DR(-/low) CD11b(+) CD33(+/high) CD14(+) CD15(-) cells) in the peripheral blood of HIV-1-seropositive subjects (n = 61) compared with healthy controls (n = 51), despite efficacious antiretroviral therapy for nearly 2 years. The elevated M-MDSC frequency in HIV-1(+) subjects correlated with prognostic HIV-1 disease markers, including the HIV-1 load (r = 0.5957; P < 0.0001), CD4(+) T cell loss (r = -0.5312; P < 0.0001), and activated T cells (r = 0.4421; P = 0.0004). Functional studies showed that M-MDSCs from HIV-1(+) subjects suppressed T cell responses in both HIV-1-specific and antigen-nonspecific manners; this effect was dependent on the induction of arginase 1 and required direct cell-cell contact. Further investigations revealed that direct HIV-1 infection or culture with HIV-1-derived Tat protein significantly enhanced human MDSC generation in vitro, and MDSCs from healthy donors could be directly infected by HIV-1 to facilitate HIV-1 replication and transmission, indicating that a positive-feedback loop between HIV-1 infection and MDSC expansion existed. In summary, our studies revealed a novel mechanism of T cell dysfunction in HIV-1-infected individuals and suggested that targeting MDSCs may be a promising strategy for HIV-1 immunotherapy.
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PMID:Expansion of monocytic myeloid-derived suppressor cells dampens T cell function in HIV-1-seropositive individuals. 2315 36


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